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The organization of the transcriptional network in specific neuronal classes.

Genome-wide expression profiling has aided the understanding of the molecular basis of neuronal diversity, but achieving broad functional insight remains a considerable challenge. Here, we perform the first systems-level analysis of microarray data from single neuronal populations using weighted gene co-expression network analysis to examine how neuronal transcriptome organization relates to neuronal function and diversity. We systematically validate network predictions using published proteomic and genomic data. Several network modules of co-expressed genes correspond to interneuron development programs, in which the hub genes are known to be critical for interneuron specification. Other co-expression modules relate to fundamental cellular functions, such as energy production, firing rate, trafficking, and synapses, suggesting that fundamental aspects of neuronal diversity are produced by quantitative variation in basic metabolic processes. We identify two transcriptionally distinct mitochondrial modules and demonstrate that one corresponds to mitochondria enriched in neuronal processes and synapses, whereas the other represents a population restricted to the soma. Finally, we show that galectin-1 is a new interneuron marker, and we validate network predictions in vivo using Rgs4 and Dlx1/2 knockout mice. These analyses provide a basis for understanding how specific aspects of neuronal phenotypic diversity are organized at the transcriptional level.

Pubmed ID: 19638972


  • Winden KD
  • Oldham MC
  • Mirnics K
  • Ebert PJ
  • Swan CH
  • Levitt P
  • Rubenstein JL
  • Horvath S
  • Geschwind DH


Molecular systems biology

Publication Data

July 29, 2009

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM08042
  • Agency: NIMH NIH HHS, Id: K05 MH065670
  • Agency: NIMH NIH HHS, Id: R01 MH49428-01
  • Agency: NIMH NIH HHS, Id: R37 MH60233-06A1
  • Agency: NIMH NIH HHS, Id: T32MH073526-01A1
  • Agency: NINDS NIH HHS, Id: U24 NS52108

Mesh Terms

  • Animals
  • Galectin 1
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Mice
  • Mitochondria
  • Neurons
  • Synapses